title: Undecylprodigiosin induced apoptosis in P388 cancer cells is associated with its binding to ribosome.
abstract: Prodigiosins (PGs) are a family of natural red pigments with anticancer activity, and one member of the family has entered clinical phase II trials. However, the anticancer mechanisms of PGs remain largely unclear. This study was designed to investigate the molecular basis of anticancer activity of UP, a derivative of PGs, in P388 cells. By introducing pharmacological inhibitors and utilizing a variety of analytical approaches including western blotting, flow cytometry and confocal laser microscopy, we found that UP inhibited proliferation of P388 via arresting cells at G2/M phase and inducing cells apoptosis, which was related to the activation of P38, JNK rather than ERK1/2 signaling. ROS regeneration and acidification in cells appear not involved in UP induced apoptosis. Furthermore, utilizing mass spectrometry, sucrose density gradient fractionation and immunofluorescence staining, we discovered that UP was apparently located at ribosome. These results together indicate that ribosome may be the potential target of UP in cancer cells, which opened a new avenue in delineating the anticancer mechanism of PGs.
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.forename: QianQun
authors.initials: Q
authors.lastname: Gu
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D012269:Ribosomal Proteins; C047347:undecylprodigiosin; D051057:Proto-Oncogene Proteins c-akt; D011353:Prodigiosin; D000111:Acetylcysteine